The purpose of this review is to summarize our current understanding of the cholesterolemic effects of individual fatty acids. Although historically there has been great interest in the fatty acid classes, it has been only recently that emphasis has shifted to individual fatty acids. Consequently, and in conjunction with the methodologic challenges inherent in studying individual fatty acids, our database is relatively modest. Nonetheless, it is clear that saturated fatty acids are hypercholesterolemic and that unsaturated fatty acids elicit a hypocholesterolemic effect compared with saturated fatty acids. The question at hand is, What are the relative cholesterolemic effects of the major saturated and unsaturated fatty acids in the diet? On the basis of a limited number of well-controlled studies, it appears that myristic acid is the most potent saturated fatty acid. Of the saturated fatty acids, stearic acid is uniquely different in that it appears to be a neutral fatty acid. Monounsaturated fatty acids appear to exert a neutral effect or to be mildly hypocholesterolemic. trans Fatty acids elicit effects that are intermediate to those of the hypercholesterolemic saturated fatty acids and the cis-monounsaturated and cis-polyunsaturated fatty acids. Polyunsaturated fatty acids elicit the most potent hypocholesterolemic effects. Studies are needed to establish the potency with which each fatty acid affects plasma total and lipoprotein cholesterol concentrations as well as the mechanisms that account for their markedly different effects. This information will be useful in making dietary recommendations for individual fatty acids that may further reduce risk of chronic diseases in the United States.